Gene Expression Profiling On Insulin Resistance And Obes

我们进行了全球基因表达谱分析，以补充正在进行的定位克隆工作，以确定糖尿病及其预测因子，胰岛素抵抗和肥胖的易感基因。为此，我们研究了非糖尿病的全血皮马印第安人使用差异显示PCR和人类寡核苷酸微阵列含有6800个基因和35000表达序列标签（EST）的组织样本中的基因表达谱。 为了确定胰岛素抵抗的可能决定因素，独立于肥胖的影响，在一组同样肥胖的Pimas的骨骼肌样本中鉴定了差异表达的基因，这些Pimas与肥胖、年龄和性别相匹配。为了确定肥胖的可能决定因素，我们从一组年龄和性别相匹配的严重肥胖和消瘦的皮马中确定了孤立的皮下腹部脂肪细胞中差异表达的基因。为了鉴定潜在的继发性差异表达的基因（例如高胰岛素血症的结果），我们 还测定了从这些相同的脂肪组织样品中生长的前脂肪细胞中的基因表达水平。 我们现在还收集了~250个骨骼肌组织样本和~150个脂肪组织样本 来自非糖尿病的皮马印第安人，并与Affyss 120万外显子阵列杂交，以确定这些组织中与2型糖尿病后期发展相关的基因表达谱。

We performed global gene expression profiling to complement the ongoing positional cloning effort to identify susceptibility genes for diabetes and its predictors, insulin resistance and obesity. To this end, we have examined gene expression profiles in tissue samples from non-diabetic full-blooded Pima Indians using differntial-display PCR and human oligonucleotide microarrays containing 6800 genes and 35000 expressed sequence tags (ESTs). To identify possible determinants of insulin resistance, independent of the effects of obesity, differentially expressed genes were identified in skeletal muscle samples from a group of equally obese Pimas, matched for obesity, age and sex. To identify possible determinants of obesity, we identified differentially expressed genes in isloated, subcutaneous, abdominal adipocytes from a group of severly obese and lean Pimas matched for age and sex. To identify genes that were potentially secondarily differentially expressed, (e.g. as a result of hyperinsulinemia), we also determined leveles of gene expression in pre-adipocytes grown from these same adipose tissue samples. We have also now collected ~250 skeletal muscle tissue samples and ~150 adipose tissue samples from non-diabetic Pima Indians and are hybridizing to Affymetrix 1.2 million exon arrays to determine the gene expresion profile in these tissues associated with later development of type 2 diabetes.